Department of Neuroscience, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
J Neurotrauma. 2012 Mar 20;29(5):766-75. doi: 10.1089/neu.2011.1754. Epub 2011 Sep 13.
Oxidative stress is a major contributor to the secondary injury process after experimental traumatic brain injury (TBI). The importance of oxidative stress in the pathobiology of human TBI is largely unknown. The F(2)-isoprostane 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), synthesized in vivo through non-enzymatic free radical catalyzed peroxidation of arachidonic acid, is a widely used biomarker of oxidative stress in multiple disease states, including TBI and cerebral ischemia/reperfusion. Our hypothesis is that harvesting of biomarkers directly in the injured brain by cerebral microdialysis (MD) is advantageous because of its high spatial and temporal resolution compared to blood or cerebrospinal fluid sampling. The aim of this study was to test the feasibility of measuring 8-iso-PGF(2α) in MD, ventricular cerebrospinal fluid (vCSF), and plasma samples collected from patients with severe TBI, and to compare the MD signals with MD-glycerol, implicated as a biomarker of oxidative stress, as well as MD-glutamate, a biomarker of excitotoxicity. Six patients (4 men, 2 women) were included in the study, three of whom had a focal/mixed TBI, and three a diffuse axonal injury (DAI). Following the bedside analysis of routine MD biomarkers (glucose, lactate:pyruvate ratio, glycerol, and glutamate), two 12-h MD samples per day were used to analyze 8-iso-PGF(2α) from 24 h up to 8 days post-injury. The interstitial levels of 8-iso-PGF(2α) were markedly higher than the levels obtained from plasma and vCSF (p<0.05), supporting our hypothesis. The MD-8-iso-PGF(2α) levels correlated strongly (p<0.05) with MD-glycerol and MD-glutamate, which are widely used biomarkers of membrane phospholipid degradation/oxidative stress and excitotoxicity, respectively. This study demonstrates the feasibility of analyzing 8-iso-PGF(2α) in MD samples from the human brain. Our results support a close relationship between oxidative stress and excitotoxicity following human TBI. MD-8-iso-PGF(2α) in combination with MD-glycerol may be useful biomarkers of oxidative stress in the neurointensive care setting.
氧化应激是实验性创伤性脑损伤（TBI）后继发性损伤过程的主要因素。氧化应激在人类 TBI 的病理生物学中的重要性在很大程度上尚不清楚。F(2)-异前列腺素 8-异前列腺素 F(2α)（8-iso-PGF(2α)），通过花生四烯酸的非酶自由基催化过氧化合成，是多种疾病状态（包括 TBI 和脑缺血/再灌注）中氧化应激的广泛使用的生物标志物。我们的假设是，通过脑微透析（MD）直接在受伤的大脑中采集生物标志物具有优势，因为与血液或脑脊液采样相比，它具有更高的时空分辨率。本研究的目的是测试在严重 TBI 患者的 MD、心室脑脊液（vCSF）和血浆样本中测量 8-iso-PGF(2α)的可行性，并将 MD 信号与 MD-甘油（一种氧化应激生物标志物）以及 MD-谷氨酸（一种兴奋性毒性生物标志物）进行比较。本研究纳入了 6 名患者（4 名男性，2 名女性），其中 3 名患者为局灶性/混合性 TBI，3 名患者为弥漫性轴索损伤（DAI）。在床边分析常规 MD 生物标志物（葡萄糖、乳酸：丙酮酸比、甘油和谷氨酸）后，每天使用两个 12 小时的 MD 样本，从损伤后 24 小时到 8 天进行分析。8-iso-PGF(2α)的间质水平明显高于从血浆和 vCSF 获得的水平（p<0.05），支持我们的假设。MD-8-iso-PGF(2α)水平与 MD-甘油和 MD-谷氨酸密切相关（p<0.05），MD-甘油和 MD-谷氨酸分别是膜磷脂降解/氧化应激和兴奋性毒性的广泛使用的生物标志物。本研究证明了在人脑的 MD 样本中分析 8-iso-PGF(2α)的可行性。我们的结果支持人类 TBI 后氧化应激和兴奋性毒性之间的密切关系。MD-8-iso-PGF(2α)与 MD-甘油联合使用可能是神经重症监护环境中氧化应激的有用生物标志物。
